Association of PTPN1 polymorphisms with breast cancer risk: A case-control study in Chinese females.

BACKGROUND: Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention.

BACKGROUND: Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear. MATERIALS AND METHODS: We conducted a case-control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size-related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis. RESULTS: Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER-)/PR negative(PR-) subtype risks, although only significantly for ER+/PR+ subtype. Waist-hip ratio was only positively correlated with ER-/PR- subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER-/PR- subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR- and positively with ER-/PR- subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER-/PR- subtype. CONCLUSION: Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER-/PR- subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals. IMPLICATIONS FOR PRACTICE: The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight-control measures may be advised in these individuals.

MicroRNA-145 inhibits growth and migration of breast cancer cells through targeting oncoprotein ROCK1.

MicroRNAs are small non-coding RNAs that may also function as oncogenes and tumor suppressor genes, as the abnormal expression of microRNAs is associated with various human tumors. MicroRNA-145 (miR-145) inhibits growth and increases chemo- or radiosensitivity in various cancers. However, the role of miR-145 in breast cancer progression remains unknown. In this study, miR-145 expression level was measured via quantitative real-time PCR in 88 pairs of human breast cancer tissues and adjacent normal tissues and in a panel of human breast cancer cell lines. Cell proliferation and cell migration were assessed by cell viability assay and transwell assay. Western blot was used to verify Rho-associated protein kinase 1 (ROCK1) as a novel target gene of miR-145. Our results showed that miR-145 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-145 in MCF-7 and BT-549 cell lines significantly inhibited cell proliferation, migration, and invasion in vitro. ROCK1 was identified as a target of miR-145, and ectopic expression of miR-145 downregulated ROCK1. Our findings indicate that miR-145 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression of breast cancer through a mechanism involving ROCK1, suggesting miR-145 as a potential new diagnostic and therapeutic target for the treatment of breast cancer.

A mini-review on factors and countermeasures associated with false-negative sentinel lymph node biopsies in breast cancer.

Sentinel lymph node biopsy (SLNB) is a new surgical technique for local axillary lymph nodes (ALNs) of breast cancer. Large-scale clinical trials have confirmed that undergoing SLNB and ALN dissection (ALND) showed no significant difference for sentinel lymph node (SLN)-negative patients in terms of disease-free survival, overall survival and recurrence-free survival. However, false-negative results are still the main concern of physicians as well as patients who undergo SLNB instead of ALND. The American Society of Breast Surgeons established a task force to suggest acceptable standards for SLNB. In 2000, the task force recommended that the identification rate for SLNB be 85% or higher and the false-negative rate be 5% or lower. This review focuses on clinical factors (tumor volume, multifocal/multi-center cancers, neoadjuvant chemotherapy and skip metastasis), tracer techniques and pathological factors affecting SLNB and explores methods for reducing the false-negative rate.

Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.

[Expression of osteopontin splice variant and its clinical significance in gastric cancer].

OBJECTIVE: To investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer. METHODS: The expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: The expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer. CONCLUSIONS: One of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.

[Analysis of clinicopathological factors associated with false-negative rate of sentinel lymph node biopsy in breast cancer patients: experience of a single center].

OBJECTIVE: The purpose of this study was to investigate the clinicopathologic factors associated with false-negative rate of sentinel lymph node biopsy (SLNB) in breast cancer, and to explore how to reduce the false-negative rate of SLNB. METHODS: The clinicopathological data of 2265 patients with invasive breast carcinoma who underwent sentinel lymph nodes biopsy (SLNB) in Shandong Cancer Hospital between November 1999 and December 2011 were retrospectively analyzed. We screened 1228 patients who received axillary lymph node dissection after SLNB, and studied the clinicopathological factors that could be associated with false-negative rate of SLNB. RESULTS: The false negative rate of this group was 10.7% (73/683), accuracy rate was 94.1% (1155/1228), and negative predictive value was 88.2% (545/618). Clinical tumor size (all P < 0.05), calendar year of surgery (all P < 0.05) and numbers of detected SLNs (all P < 0.05) were significantly related with false negative rate and accuracy rate of SLNB, determined by single factor analysis. Logistic regression model analysis showed that calendar year of surgery (P = 0.034) and numbers of detected SLNs (P = 0.012) were independent predictive factors for the false negative rate of SLNB. CONCLUSIONS: False negative rate and accuracy rate of SLNB are significantly related to the calendar year of surgery and number of detected SLNs. Strict case selection, standard operation procedure, increaseing numbers of detected SLNs, and improvement of the skill of operators are effective measures to reduce the false negative rate of SLNB.

[Value of sentinel lymph node metastasis status in predicting the presence of residual disease in the non-sentinel lymph node of breast cancer patients].

OBJECTIVE: To explore the value of sentinel lymph nodes (SLN) metastasis status in predicting the presence of residual disease in non-sentinel lymph nodes (nSLN) and the feasibility of avoiding or reducing the scope of axillary lymph node dissection (ALND) for patients with single positive SLN. METHODS: A retrospective study was conducted for 2265 patients with invasive breast carcinomas undergoing sentinel lymph nodes biopsy (SLNB) at Shandong Cancer Hospital between November 1999 and December 2011. And 1228 patients with axillary dissection were screened and divided into 5 groups of (-), (1/n), (1/1), (n/N), (n/n) (n ≥ 2, N ≥ 3, N > n) according to the status of SLN metastasis. RESULTS: The nSLN metastasis rate of SLN(-), (1/n), (1/1), (n/N) and (n/n) groups was 11.8%(73/618), 25.2%(65/258), 49.6%(67/135), 48.4%(60/124)and 65.6%(61/93)respectively. A comparison of SLN(-), (1/n), (1/1), (n/N), and (n/n) groups of nSLN metastasis showed a significant difference (P = 0.000). The differences of nSLN metastasis between SLN(-) and other groups (including 1/n, 1/1, n/N, n/n group) were significant (P = 0.000). This difference was also significant between SLN (1/n) and other positive groups (include 1/1, n/N, n/n group) (P = 0.000), but not significant between SLN(1/1), (n/N) and (n/n) groups (P = 0.842, 0.017, 0.042 respectively, Chi-square segmentation). No significant difference existed between axillary lymph node metastasis on Level II and III of SLN 1/n group and SLN(-) group (P = 0.012, 0.570,χ(2) segmentation). CONCLUSIONS: The status of SLN metastasis is one of influencing factors for the nSLN metastasis of patients with invasive breast cancer. The possibility of non-sentinel lymph node involvement for patients with single SLN metastasis was smaller than that of other SLN-positive patients. It is safe for some SLN 1/n patients to undergo low lymph node dissection. But ALND is not avoided for patients with single positive SLN (SLN 1/n n ≥ 2). Their clinicopathological variables should be also considered.

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.

BACKGROUND: Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk. METHODS: In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database. RESULTS: There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data. CONCLUSION: Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

[Systematic review of validation phase of breast cancer sentinel lymph node biopsy results in China].

OBJECTIVE: To explore the studies and application status of sentinel lymph node biopsy (SLNB) in breast cancer in China by statistically analyzing the relevant domestic literature. METHODS: The literatures published from January 1999 to December 2005 were searched in the databases of China, Info, CBM and CNKI retrieval system with "breast tumor, SLN and SLNB" as the key words. A total of 88 manuscripts were selected with 2 new reports of SLNB. The successful rate, accuracy, false-negative rate and sensitivity of SLNB were analyzed by SPSS 10.0 statistical analysis software. RESULTS: Among a total of 6282 patients, the detection rate of SLNB was 90.82% (5705/6282) and the overall false-negative rate 9.69% (259/2671). The prediction sensitivity, specificity, false positive rate, accuracy, negative and positive predictive value of SLN for axillary lymph nodes status were 90.30%, 99.64%, 0.41%, 86.52%, 92.11% and 99.55% respectively. CONCLUSION: SLNB can accurately predict the axillary lymph node metastasis. And its detection rate is correlated with patient age and tumor location. The detection rate and false-negative rate has nothing to do with the tracer injection site. A combined regimen has a higher detection rate and a low false negative rate. Affecting the whole breast, SLN is not correlated with a particular area of breast. The validation phase of SLNB in breast cancer is currently feasible in China.

Relationship Between Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

A novel tumor suppressor gene RhoBTB2 (DBC2): frequent loss of expression in sporadic breast cancer.

RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cancer patients and normal controls and cell samples from cell lines were collected and reverse transcription (RT)-PCR was used to monitor the presence of RhoBTB2 mRNA. The protein expression of RhoBTB2 was detected by immunohistochemical staining. Cumulative survival time was assessed by the Kaplan-Meier method and Cox regression model. We discovered that RhoBTB2 expression was lacking in a breast ductal epithelial carcinoma cell line T-47D but was expressed in other types of tumor cell lines and normal tissues we tested. The results from tissue samples showed that RhoBTB2 was absent in 60% of breast cancers on both the mRNA and protein level. The results from RT-PCR were completely uniform with those from immunohistochemistry. We demonstrated that loss of RhoBTB2 more frequently occurred in postmenopausal patients of age >or=50 yr old and in patients with infiltrating ductal carcinoma of the breast. The prognostic value of RhoBTB2 in breast cancers also be assessed by a long-term follow-up investigation and we found that patients with RhoBTB2-negative breast cancer were linked to poor clinical prognosis. Therefore, the loss of RhoBTB2 expression is a common occurrence in breast cancers and it is an important factor in the development and prognosis of sporadic breast cancer.

[Expressions of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma and their relationship with clinicopathological factors].

OBJECTIVE: The purpose of this study was to explore the clinical significance of expression of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma. METHODS: Semi-quantitative reverse transcriptive polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the three genes in tumor tissues from 60 patients with primary breast cancer and normal breast tissues of 30 cases. The relationship between gene expression and clinicopathological factors were analyzed and determined. RESULTS: The relative expression levels (gray scale ratio between target gene and internal reference gene) of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma tissues were 0.699 +/- 0.285, 1.045 +/- 0.302 and 0.625 +/- 0.160, respectively. In the normal breast tissues, they were 0.502 +/- 0.178, 0.418 +/- 0.140 and 0.843 +/- 0.218, respectively. There were statistically significant differences of the expression of those three genes between carcinoma tissues and normal breast tissues (P < 0.01). The expression level of Fas in carcinoma tissues was significantly higher in lymph node matastasis positive patients (0.782 +/- 0.313) than that in node-negative patients (0.557 +/- 0.146, P < 0.01). The expression level of CTLA-4 gene in carcinoma tissues was lower in II stage patients (0.978 +/- 0.330) than that in III stage patients (1.134 +/- 0.240, P < 0.05). The expression level of RhoBTB2 gene was lower in invasive ductal carcinoma (0.597 +/- 0.157) than that in invasive lobular carcinoma (0.717 +/- 0.145, P < 0.05). There were no correlations of expression of the three genes at mRNA level and age, ER, PR, HER2 status and survival time. Furthermore, no correlation was seen among the three genes expression (P > 0.05). CONCLUSION: The expression of all the three genes at mRNA level is involved in genesis and progression of breast cancer. There exist correlations between Fas expression and axillary lymph node matastasis, CTLA-4 expression and disease stage, and RhoBTB2 expression and pathological type of breast cancer.

Tumor suppressor p53 induces miR-15a processing to inhibit neuronal apoptosis inhibitory protein (NAIP) in the apoptotic response DNA damage in breast cancer cell.

This study was aimed to investigate the functional role of miR-15a in breast cancer cells in response to DNA damage and to illustrate the possible potential underlying molecular mechanism(s). Human breast cancer cell lines MCF-7 cells and/or MDA-MB-231 cells were pre-treated with or without bleomycin. Cells were transfected with corresponding vectors. qRT-PCR was used to detect the expression of mRNA or miRNA, and immunoprecipitation and immunoblot analysis were performed to explore the status of protein association. Cell apoptosis was analyzed with flow cytometry. The results showed that neuronal apoptosis inhibitory protein (NAIP) was negatively regulated by p53 in MCF-7 cells, and NAIP expression was still high in bleomycin-treated MCF-7 cells. In addition, we observed that miR-15a expression was regulated by p53, and the effects of miR-15a on DNA damage was also mediated by p53. Furthermore, the results revealed that the cell apoptosis was mediated by miR-15a. Taken together, this study reveals that p53 negatively regulates NAIP expression by targeting miR-15a processing from primary into precursor miRNA in breast cancer.

miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer.

Cancer stem cell (CSC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in tumor cell invasion and metastasis. They have been shown to occur in resistance to tamoxifen. Moreover, microRNAs (miRNAs) have been associated with CSCs, EMT as well as tamoxifen resistance. Studying molecular mechanism of CSCs, EMT as well as tamoxifen resistance will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that miR-375 inhibits CSC traits in breast cancer MCF-7 cells. Bioinformatics analysis and experimental validation identified HOXB3 as a direct target of miR-375. Overexpressing miR-375 degraded HOXB3 mRNA in MCF-7 cells. Moreover, overexpression of HOXB3 induced formation of CSC phenotypes, EMT and tamoxifen-resistance as well as enhanced ability of migration and invasion in MCF-7 cells. Most ER-positive breast cancer-related deaths occur, because of resistance to standard therapies and metastasis, restoring miR-375 or targeting HOXB3 might serve as potential therapeutic approaches for the treatment of tamoxifen-resistant breast cancer.

A case-control study on risk factors of breast cancer in Han Chinese women.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P<0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

[Expression of CD80, CD86, TGF-beta1 and IL-10 mRNA in the esophageal carcinoma].

OBJECTIVE: To investigate the correlation of CD80 and CD86 mRNA expression with the expression of transforming growth factor-beta1 mRNA (TGF-beta1) and interleukin-10 mRNA (IL-10) in the esophageal cancer. To explore the reason of impaired immunological function of dentritic cell (DC) and the mechanism of cancer cell escaption from body immunity system in the esophageal cancer patient. METHODS: Expression of CD80, CD86, TGF-beta1 and IL-10R mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in specimens of 62 esophageal carcinoma and 16 normal esophageal mucosal tissues used as normal control. RESULTS: Expression of CD80 and CD86 mRNA in the esophageal cancer tissue was significantly lower than that in the normal esophageal mucosal tissue (CD80: P = 0.038; CD86: P = 0.0002). It was significantly higher in stage I or II than that in stage III or IV (CD80: P = 0.029; CD86: P = 0.045); and also higher in paitents with high or moderate differentiation than that with poor differentiation (CD80: P = 0.046; CD86: P = 0.044). Furthermore, it was found to be reversely correlated with expression of TGF-beta1, IL-10 mRNA by multiple regression analysis (P = 0. 0001) respectively, the more TGF-beta1 and IL-10 mRNA expressed in the tumor tissue, the less CD80 and CD86 mRNA expressed by dendritic cells. CONCLUSION: The expression of CD80 and CD86 mRNA in the tissues of esophageal cancer are found to be weak, and reversely correlated with the expression of TGF-beta1 and IL-10 mRNA. High level expression of TGF-beta1 and IL-10 mRNA may be an important influential factor to the weak expression of CD80 and CD86 mRNA, which may be one of the reasons leading to impaired function of dendritic cells and immune escape of cancer cells in the esophageal cancer patient.

[Flow cytometric quantitative analysis of multiple tumor suppressor gene 1 (MTS1) and cyclooxygenase-2 (COX-2) gene expressions in invasive breast cancers and their clinical significance].

OBJECTIVE: The purpose of the present study was to explore the expression and clinical significance of multiple tumor suppressor gene 1 (MTS1) and cyclooxygenase-2 (COX-2) gene in invasive breast cancers. METHODS: Flow cytometry was used to analyze the expression level of MTS1 and COX-2 in cancer tissues and corresponding para-cancer tissues from 66 cases of primary invasive breast cancers. RESULTS: In breast cancer tissues, the expression of MTS1 and COX-2 assessed by relative fluorescence intensity were 0.84 and 10.54, respectively, and were 1.61 and 4.00 in corresponding para-cancer tissues, respectively. There was a significant difference between MTS1 and COX-2 expressions in cancer and corresponding para-cancer tissues (P <0.05). The differences of MTS1 and COX-2 expression of different ages, pathological types, tumor sizes or clinical stages of the breast cancer patients were not significant (P > 0.05). The MTS1 and COX-2 expressions were 1.12 and 5.94, respectively, in lymph node metastasis positive patients, and 0.79 and 13.05, respectively, in lymph node metastasis negative patients. The differences were significant (P <0.05). CONCLUSION: The preliminary research results suggest that MTS1 and COX-2 gene expressions play fairly important role in tumorigenesis and progression of breast cancers. MTS1 and COX-2 protein expressions have correlation with lymph node metastasis. This study provides theoretical basis for use of COX-2 selective inhibitors in prevention and treatment for breast cancer patients.